Mechanical Modulation of Fracture Healing and Implications for Skeletal Tissue Engineering - Engineered Bone: Tissue Engineering Intelligence Unit - page 78

The Influence of Fixation Stiffness on Progression of Indirect Repair
The degree of motion may influence the rate of progression of healing and the volume and
distribution of callus. The repair process is also affected by the size of the fracture gap. A critical
size defect in either a clinical fracture with bone loss or an experimental osteotomy may prevent
osseous unions leading to a nonunion or pseudarthrosis. 37 However, in many in vivo models of
bone healing a noncritical osteotomy gap is used to allow a greater ability to investigate the
influence of mechanical and biological stimuli on the repair process.
The level of motion at the fracture site is determined by the load applied through the
fracture, the geometry of the fracture line and the stiffness of the fixations system. This micro
motion is also an important factor in controlling the rate of progression of fracture healing.
There also appear to be a relationship between initial load-bearing, fixation stiffness and pro-
gression of healing. High stiffness fixation devices induce high levels of initial load-bearing but
reduce levels of micro-motion at the fracture site leading to a low rate of progression of repair.
Conversely, a lower stiffness fixation device allows greater inter-fragmentary motion which
stimulates callus formation but reduces initial ground reaction force. This suggests a
mechano-sensory mechanism within the fracture callus which forms a biofeedback control. 30
It is possible that individual variability in such a control system may account for some of the
variability in progression of repair in both experimental and clinical fracture healing.
Changes in the fixator stiffness influence the self regulated interfragmentary motion and
changes in the magnitude of inter fragmentary motion in the initial stages of the repair process
appear to influence the progression of repair. In a controlled study the use a low compliance
single sided fixation system and an osteotomy gap of 3 mm, compared to an identical but
higher compliance system, resulted in a greater magnitude of self imposed interfragmentary
cyclical displacement in the early stages of repair. With the progression of repair the
inter-fragmentary displacement reduced in both groups as a function of time becoming equiva-
lent between groups at six weeks post-operatively and did not show any difference between the
two groups up to the end point at ten weeks postoperatively. All other aspects of fixation were
controlled between the two groups. However, the outcome in terms of both radiological and
mechanical progression of healing was significantly greater in the low compliance fixator group.
This suggests the importance of mechanical environment in terms of level of inter-fragmentary
displacement in the early stages of the repair process. 29 Using a rigid fixation system in which
the axial displacement induced by weight bearing was 0.06 mm in an osteotomy gap of 0.6
mm, a defined displacement, activated by weight bearing, of 0.15-0.34 mm, was permitted in
the dynamised group and compared to the control nondynamised group Claes et al (1995), 17
showed the healing of a transverse osteotomy was enhanced by dynamisation.
The degree of compliance can also affect the progression of tissue differentiation in terms of
the distribution of tissue types and the progression of angiogenesis. Claes et al (2002), 14 com-
pared two groups of sheep in which the fixators allowed a displacement of 1mm and 0.5 mm
with an osteotomy gap of 2 mm. At the end point of nine weeks there was a greater amount of
fibrocartilage and a reduced amount of bone with the larger displacement group. Thus the
small difference in level of inter-fragmentary motion modulated the progression of indirect
bone repair. The influence of fixator stiffness and thus inter-fragmentary motion on bone
healing has also been related to consolidation of the regenerate bone following experimental
distraction osteogenesis. Here the fixator stiffness in relation to development of increased re-
generate bone density was examined and it was found that an optimal level of inter-fragmentary
displacement was evident with greater levels inducing an appearance of hypertrophic non-
union. 15
The evidence that micro motion at the fracture site is important in stimulating the biologi-
cal process has been apparent for some time. The strength of the fixation system may, therefore,
not relate to the optimum environment to stimulate effective healing although a strong fixa-
tion does provide short term functional activity. A study comparing the relation between strength
of fixation and progression of repair in a triple osteotomy model, supported the use of a